Metabolic syndrome, a condition thought to be caused by a combination of obesity, sedentary lifestyle, diet and genetics, has been found to increase the risk for cardiovascular disease and type 2 diabetes. The main characteristics of this syndrome are abdominal obesity, atherogenic dyslipidemia (elevated blood triglycerides, reduced HDL cholesterol), elevated blood pressure, insulin resistance (IR) (with or without glucose intolerance), prothrombotic and proinflammatory states and endothelial dysfunction. During the past 20 years, metabolic syndrome has become highly prevalent in North America, currently affecting an estimated 50% of the population older than 60 years.
Insulin resistance, one of the characteristics of metabolic syndrome, is defined as an impaired ability of insulin to stimulate glucose uptake and lipolysis and to modulate liver and muscle lipid metabolism. In animals and humans, insulin resistance syndrome leads to compensatory hyperinsulinemia and to various defects in lipid metabolism such as enhanced secretion of atherogenic, triacylglycerol-rich very low-density lipoproteins (VLDL), increased liberation of nonesterified fatty acids (NEFA) from adipose tissue and increased accumulation of triacylglycerols in the liver.
Current therapies in prevention and treatment of type 2 diabetes include diet and drugs. Dietary strategies designed to diminish the risk of heart disease associated with insulin resistance syndrome and type 2 diabetes are currently not well established. The most common approach is the recommendation to lower intake of total calories, especially fat and sugar, and to increase intake of fibers. The typical pharmacologic approach to the treatment of this disease focuses on drugs targeting obesity, glucose-lowering medications (e.g., metformin and acarbose) and more recently, insulin sensitizers such as PPAR-α and PPAR-γ activators, fibrates and thiazolidienodiones (TZDs). Unfortunately, therapies involving existing drugs have limited efficacy or tolerability and show significant side effects. There exists a need to provide a safe and effective method of treating metabolic syndrome and the diseases associated with it.
In the United States alone, approximately 24 million people suffer from diabetes with approximately 1.3 million being diagnosed with the disease each year. An aging population, rising obesity rates and an increasingly sedentary lifestyle have been attributed to the increase in incidence and prevalence. Furthermore, a rapid increase of type 2 diabetes in persons 30-39 years of age and in children and adolescents has been of special concern. Global prevalence rates are expected to increase from 6.4% and 285 million in 2010 to 7.7% and 439 million by 2030.
Clinical treatment goals for type 2 diabetes are directed towards lowering blood glucose levels to forestall diabetes related complications. More recently, the use of pharmacotherapies and their negative impact on cardiovascular risk have caused concern over available treatment modalities. An increased risk of myocardial ischemia has been identified with thiazolidinedione use, while earlier studies have linked Sulphonylureas to increased cardiovascular risk. Of further concern have been the contrasting outcomes of the ACCORD study which reported that lowering blood glucose to normal levels was associated with increased mortality, but the ADVANCE study did not report such findings. Such controversies in the results may suggest that treatment strategies for type 2 diabetes are not fully understood.
This begs the question if improving glycemia is sufficient to provide clinical merit in the treatment algorithm for diabetes. Currently, several therapeutic strategies include metformin in the management algorithm for type 2 diabetes with mono, di and tri therapy needing to be added to the algorithm. Therapies involving existing pharmaceuticals have limited efficacy or tolerability and show significant side effects. Many of the side effects of pharmaceuticals are thought to be associated with nutritional deficiencies caused by medications taken over a period of time ultimately resulting in a cascade of biochemical changes due to drug associated nutrient depletion. Unfortunately, long term treatment with metformin has been reported to cause vitamin B12 deficiencies. Despite the available treatment modalities, the risk of cardiovascular events has increased 2-4 fold in patients diagnosed with type 2 diabetes. As a patient's beta cell function declines, intensified treatment beyond the initial monotherapy regimen is required. The prevalence of obesity is also a concern in these patients and is thought to be a driver of cardiovascular events.
The “State of Diabetes in America” report on diabetes management evaluated current management strategies and found that, despite advances in diabetes care, blood sugar levels of millions of Americans were not controlled putting them at risk of diabetes related complications. It is possible that effective combination therapies that consist of pharmaceutical drugs and nutraceutical products may provide a new treatment algorithm that would be beneficial to diabetic patients who do not respond to drug therapy alone.
A 2005 report from the American Association of Clinical Endocrinologists (AACE) stated that 2 out of 3 Americans with type 2 diabetes did not achieve the AACE recommended blood sugar control goal of ≦6.5%. Nationally, an average of 67% of people with type 2 diabetes had blood sugar levels exceeding the AACE recommended goal. These numbers have a direct impact on cardiovascular disease risk factors for this population of subjects. NHANES 1999-2000 reported that only 7.3% of all adults diagnosed with type 2 diabetes were within acceptable range for the cardiovascular disease risk factors of HbA1c, blood pressure and total cholesterol. The American Association of Clinical Endocrinologists (AACE) acknowledges the importance of nutritional medicine in medical practice and in their guidelines identifies “complementary” or “integrative nutritionals” as products that may be used in combination with FDA approved therapies.
Needs exist for compositions and methods that provide anti-diabetic and anti-hyperlipidemia benefits to diabetic subjects currently on medication but not meeting ACCE and ADA recommended targets for blood glucose, HbA1c, blood pressure and total cholesterol.